Tropomyosin position on F-actin revealed by EM reconstruction and computational chemistry
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AuthorsLi, Xiachuan Edward
Tobacman, Larry S.
Mun, Ji Young
Craig, Roger W.
UMass Chan AffiliationsDepartment of Cell Biology
Document TypeJournal Article
Image Processing, Computer-Assisted
Reproducibility of Results
MetadataShow full item record
AbstractElectron microscopy and fiber diffraction studies of reconstituted F-actin-tropomyosin filaments reveal the azimuthal position of end-to-end linked tropomyosin molecules on the surface of actin. However, the longitudinal z-position of tropomyosin along F-actin is still uncertain. Without this information, atomic models of F-actin-tropomyosin filaments, free of constraints imposed by troponin or other actin-binding proteins, cannot be formulated, and thus optimal interfacial contacts between actin and tropomyosin remain unknown. Here, a computational search assessing electrostatic interactions for multiple azimuthal locations, z-positions, and pseudo-rotations of tropomyosin on F-actin was performed. The information gleaned was used to localize tropomyosin on F-actin, yielding an atomic model characterized by protein-protein contacts that primarily involve clusters of basic amino acids on actin subdomains 1 and 3 juxtaposed against acidic residues on the successive quasi-repeating units of tropomyosin. A virtually identical model generated by docking F-actin and tropomyosin atomic structures into electron microscopy reconstructions of F-actin-tropomyosin validated the above solution. Here, the z-position of tropomyosin alongside F-actin was defined by matching the seven broad and narrow motifs that typify tropomyosin's twisting superhelical coiled-coil to the wide and tapering tropomyosin densities seen in surface views of F-actin-tropomyosin reconstructions. The functional implications of the F-actin-tropomyosin models determined in this work are discussed. rights reserved.
SourceBiophys J. 2011 Feb 16;100(4):1005-13. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/26424
Related ResourcesLink to Article in PubMed